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For the first time, researchers found blood biomarkers for Alzheimer’s disease that correlated with minor cognitive differences in midlife adults who did not have dementia. The study, led by UC San Francisco, also found that the biomarkers, which measure tau and amyloid plaque, were associated with a greater chance of cognitive decline in these participants.
The study published May 28 in The Lancet and is primarily funded by the National Institutes of Health (NIH).
Six percent of 1,350 participants, who were aged 53 to 69, had a high level of amyloid and tau in their blood, hallmarks of Alzheimer’s, the researchers found. These proteins were linked with lower scores in two key cognitive areas.
“Alzheimer’s disease pathology begins years before symptoms emerge,” said senior author, Kristine Yaffe , MD, vice chair in the UCSF Department of Psychiatry and Behavioral Sciences. “Detecting the disease early means patients can target modifiable risk factors and maybe seek other care.”
Yaffe has led U.S. research on modifiable risk factors — like physical and cognitive inactivity, depression, cigarette smoking, heart health — and their role in dementia. Up to 40% of dementia cases could be delayed or prevented by addressing these risk factors, according to Yaffe, who is also a professor of psychiatry and behavioral sciences, neurology, and epidemiology and biostatistics.
Delayed processing speed, executive function may be earliest signs
At baseline, participants with the high biomarkers had lower processing speeds — the ability to respond quickly to changing information, such as to traffic signals or conversation — and lower executive function, which involves planning, organizing, and staying on track, and is used in tasks like arranging a schedule or handling finances.
When tested five years later, the high biomarker group had about 2.5 to 4 times the risk of rapid decline in verbal memory and around 3 to 4 times the risk of rapid decline in processing speed, indicating an increased likelihood of developing Alzheimer’s.
The participants were long-term enrollees of the multisite CARDIA study. Some 58% were women; 45% were Black, and the rest were white.
Unlike widely available methods for detecting tau and amyloid, like brain scans or spinal fluid tests, blood tests are inexpensive and noninvasive. They are currently FDA-approved for patients with symptoms but could eventually include those without symptoms, said Yaffe.
These blood tests should be used with caution, Yaffe added. “There’s a possibility of false positives and they can only be used for Alzheimer’s, not other dementias, meaning about 60% to 70% of all dementia cases,” Yaffe stated. “But for some people who discover they have the biomarkers, testing could open a window to embark on interventions that may postpone Alzheimer’s onset.”
Authors: First author is Xiaqing Jiang, PhD, formerly of the UCSF Department of Psychiatry and Behavioral Sciences. For other authors, please see the paper.
Funding: National Heart, Lung, and Blood Institute contracts (75N92023D00002, 75N92023D00003, 75N92023D00004, 75N92023D00005, and 75N92023D00006); National Institute on Aging (R01AG063887 and R01AG09143); Alzheimer’s Association Research Fellowship (AARFD-23-1150636 and NIA R35AG071916, R01AG063887, R01AG091431, and 1K99AG083211).
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The Lancet